We have made a variety of conjugate vaccines in which gp 120 was covalently linked to a carrier protein, such as hepatitis B surface antigen or tetanus toxoid. However, up to now, we have lacked a small animal that was unresponsive to gp 120, to measure the carrier effect on immunogenicity. We have found a genetic low responder mouse. On an A background, we found a hierarchy of H-2 types, with k.b.x. Using this last combination, we find little or no antibodies made in response to two does, with the difference from high responders reaching a p value of <003. We then immunized low responder animals with a conjugate of gp 120 linked to CRIM protein. In this case, the antibody response was slightly greater than for the high responder mice immunized to gp 120 alone. Thus, this animal provides a model for quickly testing a variety of gp 120 conjugates for enhanced immunogenicity due to carrier effect. We will now test a variety of carrier proteins, reserving the best ones will be tested in primates and man. The resulting antibodies will be tested by ELISA assay initially, and for neutralizing activity against T cell tropic virus and also against macrophage tropic virus, using a new HeLa cell line expressing both CD4 and CKR-5 receptors.